Defective Repair Of Neuronal Activity-induced DNA Double Strand Breaks: A Novel Pathogenic Mechanism For Neurodegeneration In Ataxia-telangiectasia
Funder
National Health and Medical Research Council
Funding Amount
$570,821.00
Summary
The reason for degeneration of the hindbrain in patients with Ataxia-telangiectasia is unknown. Firing of neurons leads to breaks in the DNA that are normally repaired by ATM, the gene defective in Ataxia-telangiectasia, and failure to reset the system likely leads to abnormal gene expression and cell death. Here we use neuronal cell types derived from patient stem cells to elucidate how this novel disease mechanism may cause hindbrain degeneration and to test drugs that can overcome this.
The C-type Lectin Mincle Exemplifies A New Mode Of Sterile Inflammation In Cardiovascular Disease
Funder
National Health and Medical Research Council
Funding Amount
$609,237.00
Summary
This project investigates two of the life-changing cardiovascular events that most commonly impact on Australians today; Heart attack and Stroke. These diseases often leave individuals debilitated with a long recovery period, and for many people the event is fatal. We have shown that blocking the action of an immune component, "Mincle", reduces the inflammation associated with stroke, and improves recovery. This project looks at what Mincle does in brain and heart muscle, and why blocking Mincle ....This project investigates two of the life-changing cardiovascular events that most commonly impact on Australians today; Heart attack and Stroke. These diseases often leave individuals debilitated with a long recovery period, and for many people the event is fatal. We have shown that blocking the action of an immune component, "Mincle", reduces the inflammation associated with stroke, and improves recovery. This project looks at what Mincle does in brain and heart muscle, and why blocking Mincle protects cells from loss of oxygen.Read moreRead less
Investigating The Apoptotic Function Of Bak And Bax
Funder
National Health and Medical Research Council
Funding Amount
$476,271.00
Summary
Proper regulation of how and when cells die is crucial for the development and maintenance of a healthy body and mind. We shall investigate the key proteins that are ultimately responsible for killing a cell with the long term view to identify ways to target these proteins for the treatment of conditions including neurodegenerative and cardiovascular diseases.
Defining The Role Of The Ubiquitin Protein Ligase Nedd4 In Vascular Development.
Funder
National Health and Medical Research Council
Funding Amount
$702,166.00
Summary
Blood and lymphatic vessels are vital components of the cardiovascular system. Abnormalities in the growth and development of these vessels are associated with human disorders including cancer and cardiovascular disease. The focus of this application is to characterise the role of the ubiquitin protein ligase Nedd4 in vascular development, with the aim of identifying targets to which novel therapeutics for the treatment of blood and lymphatic vascular diseases could be generated.
Understanding Human Dysmorphology Through Analysis Of ENU Mutant Mice
Funder
National Health and Medical Research Council
Funding Amount
$602,501.00
Summary
Birth defects are common and have an enormous impact on both the individual and their family. Birth defects are by definition the products of abnormal development of the embryo. Our research is aimed at identifying the normal mechanisms that usually prevail during development and the disturbances to those mechanisms that result in birth defects. These findings will lead to improved diagnostic, therapeutic and preventative options for families affected by birth defects
Rapid Identification And Characterisation Of Genes Involved In Skeletal Development
Funder
National Health and Medical Research Council
Funding Amount
$550,536.00
Summary
Birth defects are common and have an enormous impact on both the individual and their family. Birth defects are by definition the products of abnormal development of the embryo. Our research is aimed at identifying the normal mechanisms that usually prevail during development and the disturbances to those mechanisms that result in birth defects. These findings will lead to improved diagnostic, therapeutic and preventative options for families affected by birth defects
The Hippo Pathway, Neural Stem Cells And Brain Growth
Funder
National Health and Medical Research Council
Funding Amount
$363,137.00
Summary
During organism development, the brain grows to the right size without overgrowing. Neural stem cells are key regulators of brain size. We will define how the Hippo pathway crosstalks with nutrition-induced signals to control proliferation of neural stem cells and brain size. As well as producing important insights into normal growth, we will increase our understanding of brain diseases associated with aberrant brain growth, such as cancer.
Dissecting The Embryonic Blood-endothelial Regulatory Code And Investigating Its Role In Leukaemia
Funder
National Health and Medical Research Council
Funding Amount
$646,389.00
Summary
Cancer initiating cells acquire stem cell characteristics and multiply within a supportive environment that helps maintain and propagate malignant cells. Identifying the normal hierarchy of gene control within blood stem cells and designing therapies that target cancer cells is the ultimate goal of this body of work.
Defining The Role Of Nedd4 In Neural Crest Cell Development
Funder
National Health and Medical Research Council
Funding Amount
$541,565.00
Summary
Neural crest cells are specialised stem cells that give rise to many tissues and organs during embryonic development. We recently identified an essential role for a regulatory protein in neural crest cells. Our research is aimed at understanding how this protein influences the growth of structures such as the heart and facial skeleton. Understanding these processes underpins the ultimate goal of implementing diagnostic and preventative medicine for highly prevalent congenital birth defects.
Defining The Role Of VEGF And Vascular Formation In Craniofacial Development
Funder
National Health and Medical Research Council
Funding Amount
$636,417.00
Summary
Aberrant neural crest cell development gives rise to common congenital malformations such as cleft lip and/or palate and cardiac outflow tract defects that effect over 1% of all births. As the aetiology of these disorders are largely unknown it is critical to understand the cell and molecular mechanisms coordinating NCC development such that alternative therapies may be devised to target the underlying pathological defects and to provide definitive diagnostic / prognostic tools.